The biochemistry of erythromycin (and other antimetabolites) and its producing organism, Streptomyces erythreus, will be investigated. Erythromycin, a macrocyclic lactone antibiotic, functions by binding to the 50S ribosomal unit and inhibiting protein synthesis. The exact mode of the erythromycin-ribosome interaction will be studied by observing the effect after chemical modifications of ribosomal constituents, and after the addition of various chemical agents known to affect specific interactions. The mechanism of bacterial resistance to erythromycin will be approached in a two-fold manner: Comparison of the initial uptake rate constants for bacteria at various stages of growth, and comparison of constituents in erythromycin sensitive and resistant ribosomes. To clarify whether the translocation step or the peptidyl synthase step is inhibited by erythromycin, experiments will be carried out with a purified functioning 70S ribosomal monomer, whose 50S unit had been previously treated or untreated with erythromycin, and purified factors necessary for translocation or peptide bond synthesis. Such experiments will provide insight into the precise mechanism or erythromycin action.